This item was digitized by the Internet Archive. Thesis (M.A.)--Boston University

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dc.description.abstract

Studies dealing with the effect of heat upon immune sera can be divided conveniently into three periods. The first period extended from the late eighteen nineties to about 1910. This was an exploratory period in which some preliminary studies of the denaturing effect of heat were made. The following facts were reported: (1) Antibodies can be destroyed by heat but the critical temperature is not the same for all antibodies (2) Antibodies present in the different fractions of serum appear to differ in their thermal lability (3) Species differences may exist with regard to the resistance of antibody to heat (4) Normal and immune antibodies may differ in their lability to heat (5) Agglutinoids and precipitoids are formed when immune sera are heated (6) Flagellar and somatic agglutinins can be differentiated by their resistance to heat (7) Certain substances, for example, urea, that prevent the coagulation of protein will prevent destruction of agglutinins (8) In many instances the destruction of antibody by heat occurs as a unimolecular reaction.
The second period in the investigation of the denaturing effect of heat upon immune sera extended from 1910 to 1935. The scope of the investigations was greater than it was during the earlier period. Some of the earlier observations were confirmed and added information uas acquired. Many factors of importance in the concentrating and purifying of therapeutic sera by the aid of heat were determined, such us, the proper temperature, the time of heating, the pH of the serum and the concentration of neutral salts. There were many investigations of the effect of heat upon flagellar and somatic agglutinins. The phenomenon of inhibition was the subject of one or more thorough studies. Conclusive evidence was presented of the specific character of inhibition by heated immune sera. Also, it was shown beyond doubt that heated nonagglutinating sera combined specifically with their antigens. The presence of inhibiting but nonagglutinating antibody was reported in a native immune serum. It was found that some heated sera retained their protective and passively sensitizing properties after the precipitating or agglutinating property was lost. Toward the end of the period substances like urea, glycerol, sucrose that prevent the coagulation of protein by heat were studied for their effect upon the denaturation of immune sera by heat. They had a protective influence on the antibody when they were added to immune sera before the sera were heated.
During the last few years the understanding of the denaturation of antibody by heat, and by other methods has been furthered by increased knowledge of the properties of proteins, serological studies, electrophoretic studies, and studies in which the ultracentrifuge was used have contributed to our knowledge of antibody. Utilization of all these methods has brought out the following facts: (1) In some immune sera denatured by various methods the antibody-globulin forms complexes with the nonspecific protein and loses its power of precipitating or agglutinating its antigen. Other serological properties such as the power to combine specifically, to inhibit, to protect, and to neutralize toxin are retained to varying degrees depending upon the extent of the denaturation.
The experimental work presented confirmed the results of others in providing evidence of the formation of complexes between antibody-globulin and serologically inert protein.
A possible explanation of tne effect of denaturation in the light of recent concepts of the structure of protein was presented.